nutrition and non-insulin dependent diabetes mellitus from...

Alternative Medicine Review ◆ Volume 2, Number 5 ◆ 1997

Copyright©1997 Thorne Research, Inc. All Rights Reserved. No Reprint Without Written Permission

Nutrition and Non-Insulin DependentDiabetes Mellitus from an Anthropological

PerspectiveC. Leigh Broadhurst, Ph.D.

AbstractHomo Sapiens is considered to be adapted to a Paleolithic hunter-gatherer diet,

and was present in anatomically modern form more than 100,000 years before theadoption of agriculture. The causative factors for non-insulin dependent diabetes mellitus(NIDDM) relate to adopting Western dietary standards based on abundant, processedagricultural foods. Ethnic minorities adopting Western diets have uniform increases inNIDDM incidence, but there are also intrinsic differences in NIDDM incidence betweenvarious ethnic groups.

Insulin sensitivity correlates positively with membrane unsaturation and omega-3/omega-6 polyunsaturated fatty acids (PUFA) in phospholipids, and negatively withintramuscular triglyceride and central obesity. Omega-3 PUFA supplementation isrecommended for NIDDM, including long-chain PUFA. Chromium (Cr) is required fornormal insulin function; however, we require more Cr than is provided by the typicalWestern diet. Cr supplementation well above the Estimated Safe and Adequate DailyDietary Intake (ESADDI) of 50-200 mcg/day may be required to prevent and treat NIDDM.In the past, Cr dietary availability is likely to have been higher, yet requirements lower.

In plant foods, many biologically active phytochemicals are bitter or astringent,so many plants have been bred to contain lower levels. Simultaneously, these foodhave become sweeter and less fibrous. Hence, consuming modern produce is notequivalent to consuming the wild precursors. Herbal products can provide thesephytochemicals and fibers. Many botanical products have benefits for controlling diabetesbeyond the inhibition of glucose absorption, including stimulating insulin secretion and/or action, improving insulin binding, improving capillary function, and preventing PUFAperoxidation.(Alt Med Rev 1997;2(5):378-399)

IntroductionNon-insulin dependent diabetes mellitus (NIDDM), or Type II diabetes is one of the

largest health problems in Western countries. NIDDM currently affects some 6–12 million personsin the US, and incidence is increasing despite continual advances in medical care. Approximately

C. Leigh Broadhurst, Ph.D.—22nd Century Nutrition, Inc.; Herbal Vineyard, Inc.; Visiting Scientist, Nutrient Requirements and FunctionsLaboratory, USDA Beltsville Human Nutrition Research Center, Beltsville, MD.Correspondence address: 22nd Century Nutrition, Inc. 1315 Harding Lane. Cloverly, MD 20905-4007. [email protected]


Alternative Medicine Review ◆ Volume 2, Number 5 ◆ 1997 Page 379

95% of diabetics are Type II, presenting withsymptoms well into adulthood. While there issome genetic propensity for development ofNIDDM, the etiology of this disease is largelynutritional. The small number of geneticfactors currently identified with NIDDM arelikely to be factors which are expressed bycurrent Western diets.1-3 No genes particularto NIDDM have thus far been identified, butthere are combinations of candidate geneswhich may confer a susceptibility towardglucose intolerance and insulin resistance.4

However, these various genetic factors maynot have led to NIDDM in the past or underother circumstances. It is crucial to understandthat unlike Type I (insulin-dependent diabetes),NIDDM is almost entirely both caused andprevented by nutritional choices, thus it isamenable to holistic alternative medicaltreatment.

The incidence of diabetes in seven U.S.ethnic minorities (for which there are data) ismuch higher than the incidence in their respec-tive countries of origin.5 This indicates whenthese groups adopt Western eating and lifestylepractices, the incidence of NIDDM increasesuniformly. This same epidemiological trendhas long been recognized for cardiovasculardisease and colon cancer.6-9

The U.S. diet provides the highestamount of calories for the lowest cost world-wide.9 It also has the highest availability oflarge-scale agricultural commodities, and re-fined and processed food products. The U.S.diet is becoming popular around the world, butis also the diet farthest removed from thatwhich Homo sapiens is considered to haveevolved eating.9-12 Broadhurst13 proposed thefollowing list, namely that the major causativefactors for NIDDM, while exacerbated by ag-ing, can all be related to a modern agricultural-processed food based diet:

1. Obesity and overfatness: In particu-lar, simultaneously increasing lean body masswith resistance training while decreasing body

fat provides significant improvement in gly-cemic control.2. Carbohydrate (especially in refined and pro-cessed forms) and fat overnutrition.3. Lack of polyunsaturated fatty acids (PUFA)in plasma membranes and unbalanced triglyc-eride intake.4. Chromium deficiency.5. Lack of soluble fiber and relevant benefi-cial phytochemicals.

Factors 1 and 2 have long been knownand researched, and will not be reviewed here.Many of the included references provide ex-tensive information on these factors. Obesityis the single largest cause of NIDDM, andovernutrition is the single largest cause of obe-sity.14-17 Physical activity is known to improveboth glucose tolerance and overfatness.15,18,19

The benefits of diets based on unrefined wholefoods versus refined foods have also beendocumented.14,20,21 Factors 3-5 are not only in-dependently significant but also synergistic,yet discussion of them is often lacking in pro-tocols for diabetes management. Hence, theyare the focus of this paper.

Paleolithic Requirements DefineOur Nutritional Needs

A concept of overriding importance inhuman nutrition is that we still have the me-tabolisms and physiologies of Paleolithichunter-gatherers. Based on the relatively slowpace of skeletal morphologic changes requiredto define a hominid genus,22-25 our fundamen-tal nutritional needs have probably changedlittle since the rise of our genus 2-2.5 millionyears ago. At a minimum, we are obliged torecognize our nutritional requirements cannothave changed significantly since the rise of ourspecies Homo sapiens in Africa between100,000 and 300,000 years ago.24-28 Extensivediscussion of this subject is beyond the presentscope, but reviews of the role of nutrition inhuman evolution can be found in refs. 9 and29-31.

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80 Alternative Medicine Review ◆ Volume 2, Number 5 ◆ 1997


The remains of anatomically modernhumans H. sapiens (var. sapiens or proto-Cro-Magnon) dating to prior to 100,000 years agohave been found in localities in southern Eu-rope and the Middle East, and modern humanswere widespread across Eurasia by 40,000years ago.26,32,33 This is a very long time ascompared to the 10,000 years since the initialadoption of agriculture, and the 50-100 yearsthat modern processed foods have been avail-able. For 99.8% of our time as genus Homowe ate exclusively wild foods.9,11,12 As far ashuman evolution and metabolism is concerned,agriculture is a new experience — we are stillin the initial stages of a grand experiment con-ducted on ourselves. Logic dictates we mustat least consider that the profound changes inour diets since the Neolithic Revolution havea role in the origin of NIDDM.

BasicComposition OfHunter-GathererDiets

Archeologicaland ethnological stud-ies have evaluated thecomposition of hunter-gatherer diets in bothprehistoric and his-toric/existing popula-tions. Preagriculturaldiets are/were depen-dent on animal proteinand fat, and wild veg-etation.10,11 With therare exception ofhoney, they never con-tained concentratedcarbohydrate sourcessuch as sugar, flour,rice, and pasta. In tem-perate and especially

colder climates, carbohydrates were exceed-ingly limited. In the extreme, traditional dietsof Arctic societies are virtually devoid of car-bohydrate.34-37 Similarly, North AmericanNorthwest coast Indians traditionally con-sumed great quantities of fat because carbo-hydrate was limited to scarce clover roots anda short berry season.38 Tropical and subtropi-cal environments provided consistently higheramount of fruits, honey, and starchy roots andtubers; however, fat and protein-rich nuts of-ten provided the largest percentage of calo-ries from plant foods34,39 Cereal grains wereunknown, as were legumes such as soybeansand kidney beans. In some environments, le-gumes may have been consumed in their greenstate; however, dried mature beans were onlyoccasionally utilized. Like cereal grains, ma-ture legumes such as soybeans require com-mercial agricultural production, and are alsototally inedible unless cooked. In addition,many wild legumes are toxic.40, 41

16:0

16:1n-7

20:0

22:0

24:0

18:1n-9

18:2n-9

20:2n-9

20:3n-9

22:3n-9

16:2n-6

18:2n-6 (LA)

18:3n-6

20:3n-6

20:4n-6 (AA)

22:4n-6

22:5n-6

16:3n-3

18:3n-3 (LNA)

18:4n-3

20:4n-3

20:5n-3 (EPA)

22:5n-3

22:6n-3 (DHA)

18:0

20:1n-9

22:1n-9

24:1n-9* *

POLYUNSATURATESSATURATES / MONOUNSATURATES

[CE]

[D]

[CE]

[D]

[CE]

[CE/D/RC]

Figure 1. Long chain fatty acid pathways in mammals.

Palmitic acid (16:0) is the starting point for saturates (18:0 to 24:0) and monounsaturates (16: ln-7 through 24:ln-9). Linoleic acid (LA, 18:2n-6) and a-linolenic acid (LNA, 18:3n-3) are the main precursors to the polyunsaturates(n-3 and n-6 PUFA series). Note also that the 16 carbon n-6 and n-3 PUFA are present in the human diet (i.e.selected green vegetables) and can be metabolised to 18:2n-6 and 18:3n-3. Pathways proceed through chainelongation [CE] and desaturation [D]. The final step in PUFA metabolism involves retroconversion [RC] from24-carbon intermediates [*] not shown. Preference by desaturase enzymes is shown by the arrowheads:



Based on ethnographic observations ofextant populations as well as archaeologicalevidence, hunter-gatherers used game, fish,shellfish, reptiles, amphibians, and insects forprotein sources. On average, total dietary fatin the hunter-gatherer diet is not considered tohave exceeded 30%en (less than 30% of thetotal caloric intake as fat); however, diets werenever fat-free, and as mentioned above, somegroups ate considerable fat. Cross-cultural eth-nographic and historical studies have repeat-edly observed that great efforts are made toseek out and consume animal protein andfat.35,42,43 In general, edible portions of wildgame, fish, and shellfish contain a greater per-centage of structural fat and protein and lessstorage fat per unit weight than does meat fromlivestock.44,45 Structural fat is typically moreroughly balanced in polyunsaturated fatty ac-ids (PUFA, including long-chain or LC-PUFA), mono-unsaturated fatty acids(MUFA), and saturated fatty acids (SFA) thanis storage fat.46,47 Storage fat usually has ahigher percentage of SFA, and meats with agood deal of intramuscular fat (marbling) haveboth higher absolute and relative amounts ofSFA per unit weight than do lean meats.

PUFA Balance And MembraneAbnormalities

Abnormal membrane phospholipidprofiles is of major significance in both TypeI and Type II diabetes.48-50 It is known that in-sulin stimulates and glucagon inhibits thedesaturase enzyme system (Fig. 1), thus in-fluencing the PUFA available for membraneincorporation. Conversely, the fatty acid com-position of membrane lipids influences theaction of insulin. Experimental data haveshown that increasing membrane fluidity byfeeding higher dietary levels of PUFA in-creases the number of insulin receptors, there-fore increasing insulin activity. In humans withType I diabetes, and in chemically-induceddiabetic animal models, insulin administration

and LC-PUFA supplementation (i.e., eveningprimrose and fish oils) can partially correct themembrane abnormalities.50,51 However, mostdiabetics are Type II, characterized byhyperinsulinemia or insulin resistance.Roughly 75% of Type II diabetics have el-evated levels of insulin, but this insulin is nottotally effective.52 Type II diabetic membraneabnormalities thus cannot be only the resultof insulin/glucagon influences on thedesaturase system; rather, the diabetic condi-tion may result from accumulating membraneabnormalities.

A recent study comparing 575 diabet-ics (242 IDDM and 333 NIDDM subjects)with 319 normal controls showed a failure toincorporate PUFA in cell membranes is a broadcharacteristic of human diabetes.53 All diabeticred cell membranes were relatively lower inPUFA, with a concomitant increase in MUFAand SFA. In IDDM patients, linoleic acid (LA)was elevated relative to its metabolites (seeFig. 1) in red cell and plasma phospholipids,triglycerides, and cholesterol esters, consistentwith a simple impairment of PUFA metabo-lism. NIDDM patients had a normal ratio ofplasma phospholipids, and elevated LA in redcell phospholipids, cholesterol esters, and trig-lyceride, although not to the degree seen inthe IDDM patients. This again indicates thatin NIDDM impaired insulin activity may beboth a cause and an effect of membrane PUFAcomposition.

Omega-6 and Omega-3 PUFABalance

Intensive research during the past 15years has firmly concluded the n-6 to n-3PUFA ratio in the current Western diet is muchhigher than is recommended.54,55 Due mainlyto the prevalence of agricultural oils such ascorn, soybean, sunflower, peanut, and cotton-seed, LA is normally greater than 85% of totaldietary PUFA.56 N-3 intake is further reducedby an estimated average intake of 13.3 gm/

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person/day trans-fats in the United States.57

This figure may be even higher, based on newanalytical techniques.58 Huang and Nassar,59

Lands et al,60 and Broadhurst13 reviewed di-etary PUFA, and concluded n-6 and n-3 fattyacids must be considered together, and mustbe balanced in the diet. Dietary PUFA balanceis necessary because n-6 and n-3 PUFA com-pete for the same desaturase and elongase en-zymes (Fig. 1). Too much n-6 inhibitsdesaturation (and to a lesser degree elonga-tion) of n-3, and vice versa. In addition, ∆5and ∆6 desaturase activity is regulated by anumber of factors, including insulin activ-ity.50,61,62 Current Western dietary guidelines forthe overall ratio in dietary n-6 to n-3 PUFAare 5-10:163 and 4:1.64 Ratios of 4:1 to 1:1 areadvocated by many researchers who have ex-amined the fatty acid composition of mamma-lian organ and neural tissues, and traditionalhunter-gatherer foods.30,31,44-46,65-67 Our currenthigh intake of n-6 PUFA (especially LA), withn-6 to n-3 ratios on the order of 15 to 45, isunprecedented in human history and prehis-tory.

Lipid nutrition, muscle membranefunction, and insulin efficiency

Diets relatively high in SFA, hydroge-nated fat, and n-6 PUFA can significantly af-fect insulin efficiency and glucose response.Skeletal muscle is the major site of insulin-stimulated glucose utilization.(footnote a) High fatdiets increase the accumulation of storage trig-lyceride in skeletal muscles (i.e.,“marbling”),which leads directly to insulin resistance in theindividual muscles.2,68 When a percentage ofn-3 PUFA is substituted for other fat in thediets of rats or humans, insulin resistance canbe improved or prevented.2,68,69 The fat com-position of muscle membrane phospholipids

reflects the combined influences of diet anddesaturase/elongase activity, and in turn thephospholipid composition affects the bindingand action of insulin. In general, the more theunsaturated (flexible; fluid) the membrane, thebetter glucose is utilized. The more saturatedthe membrane, the more deleterious the effecton insulin efficiency.68,70 This does not meanNIDDM cannot develop if membrane fluidityis normal, but rather that PUFA metabolismhas a greater or lesser role in NIDDM depend-ing on an individual’s diet and genetics.71

For example, insulin-stimulated glu-cose metabolism was low in genetically obeserats fed a high fat, n-3 deficient diet, but re-turned to normal when n-3 LC-PUFA (fish oil)was added to the diet. The rats’ metabolic ratealso increased significantly.72 Similar resultswere seen in streptozotocin-induced diabeticrats on high fat diets, where higher ratios ofPUFA to SFA in various diet groups was asso-ciated with improved insulin binding.61 Nor-mal rats fed high fat diets all became insulinresistant with high SFA, MUFA, and LA di-ets, with SFA causing the most deteriorationand LA causing the least.49 Substituting 11%of fat with n-3 LC-PUFA from fish oil com-pletely normalized insulin function. A similarreplacement with n-3 as alpha-linolenic acid(LNA) from flaxseed oil normalized insulinfunction in the SFA diet group, but was inef-fective in the LA group.

Results from adult human studies areconsistent with those from rodents. In threedifferent studies, (Caucasian Australian, Cau-casian Swedish, Arizona Pima Indians) musclebiopsies obtained during surgery were corre-lated with fasting glucose or euglycemic clamptests. In all studies, the higher the degree ofmembrane saturation, the more insulin-resis-tant the individual.68,69 Both hyperglycemic andnormoglycemic individuals were studied.

Earlier concerns that fish oilsupplementation might cause elevated glucoselevels in diabetics, purportedly by reducinginsulin secretion, have not been confirmed by

a Different types of muscle fibers also differ in their insulinsensitivity, with type I (slow twitch oxidative) and to a lesserextent type IIa (fast twitch oxidative) more sensitive than typeIIb (fast twitch glycolitic).73,74



recent research.69,75 Sirtori et al conducted alarge (n=935), multi-center, double-blind studyon hypertrigylceridemic subjects, and foundplasma triacylglycerol decreased up to 21.5%with modest supplementation of n-3 LC-PUFAas ethyl esters.75 In addition tohypertriglyceridemia, 55% of subjects hadNIDDM or impaired glucose tolerance, and68% had arterial hypertension. Subjects weregiven 1530 mg EPA and 1050 mg DHA dailyfor two months, then decreased to 1020 mgEPA and 700 mg DHA daily for the followingfour months. Placebo subjects received oliveoil. No effects on glycemic control or bloodpressure were recorded, and those withNIDDM had proportionally greater decreasesin triacylglycerols and increases in HDLcholesterol.

It is important to make the distinctionbetween fat either stored or used as a substratefor energy metabolism, and structural fat —most importantly the structural fat containedin the cell membranes of insulin-sensitive tis-sues. Provided energy balance is maintained,high MUFA diets have shown the potential tobe broadly beneficial for diabetics, especiallyif monoenes are substituted isocalorically forcarbohydrates or SFA.17,76-78 In these cases,MUFA is provided for energy, and the under-lying assumption is that structural PUFA arenot deficient. This contrasts with the rodentstudies above (and other such studies), wherethe animals are purposely raised to be PUFA-deficient. The imposition of PUFA deficiencyis not ethical for human experimentation, butpossible nonetheless through self-imposed di-etary choices. The question relating to the fatcontent of hunter-gatherer diets and the originof NIDDM is not simply: “Which dietary fatscan best ameliorate existing diabetes?” butmore importantly: “Is the profound loss of n-3 LC-PUFA and/or imbalance in triglyceridetypes in the current Western diet a potentiallypreventable cause of NIDDM?”

In the latter case we must consider thepotential effects on structural fat of a lifetime

of consuming dietary fats composed mainlyof SFA, LA, and trans-fats. It is interesting tonote that in a crossover diet study, Christiansenet al found that trans-monoenes were notbeneficial for diabetics.78 Sixteen obeseNIDDM patients were fed 20%en of eithertrans-MUFA, cis-MUFA, (i.e., oleic acid), orSFA in a diet with 30%en from fat overall, with6 weeks for each diet type. Both SFA andtrans-MUFA increased postprandial insulinand C-peptide secretion, but cis-MUFA hadno effect. Serum glucose and lipids were notsignificantly different in any of the groups,which may indicate reduced insulin sensitivityin the SFA and trans-MUFA groups.

PUFA balance, central obesity, andinsulin efficiency

Central obesity is associated with ahigh incidence of NIDDM as well as cardio-vascular disease, hypertension, and prematuremortality. Abdominally-obese individuals tendto have a diminished capability to utilize glu-cose peripherally, or extract insulin during itsfirst portal passage. They also have increasedcirculating free fatty acids (which reduces glu-cose metabolism), and a decline in insulin re-ceptor number.79 Two populations prone tocentral obesity, Arizona Pima Indians 80,81 andSouth Asian Indians,82 appear to have a ge-netic predisposition for NIDDM. However, itis acknowledged that widespread health prob-lems did not arise until these populationsadopted Western food shopping and dietaryhabits. According to Szathmary,3 NIDDM wasvirtually unknown in North American aborigi-nal populations before 1940.

Dramatic increases in calories, refinedcarbohydrates, total fat, and n-6/n-3 PUFAratios have affected these populations. In boththe Australian and Pima subjects above, in-creasing n-6/n-3 ratios correlated positivelywith obesity and insulin resistance. However,the Pimas had much lower n-3 PUFA in theirmembrane phospholipids than Australian or

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especially Swedish subjects.81 In the case ofthe Australians versus the Pima, Pan et al foundlittle evidence for greatly differing dietary in-takes; however, the average docosahexaenoicacid (DHA) content of muscle phospholipidswas 2.5±0.7% versus 1.2±0.1%, respectively.2

This situation for the native Americanpopulation overall probably reflects both de-creased dietary intake and decreaseddesaturase/elongase activity. In the Pima stud-ied by Pan et al,2 both impaired insulin actionand obesity were found to be independentlyrelated to reduced ∆5 desaturase activity.Vancouver Island Canadian natives andGreenland Eskimos, closed-society groupsaccustomed to traditional marine diets, havebeen shown to have a limited ability to con-vert 18-carbon PUFA to LC-PUFA, which islikely to be genetic.83 The overall incidence ofNIDDM in the Pima is the highest of any eth-nic group known (50%), and specific geneticfactors may play a role. For example, the Pimaexhibit a small intestine fatty acid binding pro-tein genotype that increases the affinity of thatprotein for long-chain fatty acids. This increasein affinity may increase the transport of fatsacross the intestine. This genotype is also as-sociated with higher mean fasting glucose lev-els, and greater insulin responses to both oralglucose and mixed meals.84 Especially disturb-ing is the observation that Pima mothers whowere diabetic during pregnancy have childrenwith a greater incidence of obesity and diabe-tes.5

South Asians living in the UK have ahigher incidence of diabetes than the EuropeanCaucasian population (19% versus 4%), anda significantly greater age-standardized coro-nary heart disease mortality. While SouthAsians are no more overweight than their Eu-ropean counterparts, the former have a markedtendency towards central obesity.82,85 The dietof South Asians has a much greater ratio ofPUFA to SFA than the typical Western diet;however, the n-6/n-3 ratio is very high. Das

found elevated lipid peroxides and decreasedplasma PUFA metabolites in 10 moderateNIDDM (no complications) and 10 severeNIDDM (unequivocal nephropathy) subjectsas compared to 20 controls.85 Lipidperoxidation was confirmed by the plasmamalondialdehyde equivalents for the threegroups: 2.4±0.6, 3.0±1.1, and 1.27±0.23, re-spectively. Both groups of diabetics had sig-nificant reductions in dihomo gamma linolenicacid and arachidonic acid from the n-6 series,and LNA and DHA from the n-3 series (seeFig. 1). This also probably reflects a combi-nation of decreased dietary LC-PUFA and n-3PUFA intake coupled with reduced desaturase/elongase activity. In addition, the observedhigh levels of peroxidation in the diabetics mayindicate destruction of PUFA as opposed toutilization.

A tendency to store fat, release insu-lin, and desaturate/elongate only the minimumamount of dietary 18-carbon PUFA metaboli-cally necessary were likely positive factors forhumans adapted to Paleolithic foods and con-stant physical activity, but might be maladap-tive today. These are adaptations to a diet (a)low in fat and often energy, (b) relatively highin n-3 PUFA, (c) raw and unprocessed, and(d) free from high density carbohydrates —often such that dietary fat rather than carbo-hydrate was an absolute requirement for en-ergy. The incidence of NIDDM in the U.S. isgreater among minorities (Asian, Black, His-panic, Native American) than Caucasians,even when diet and lifestyle factors are takeninto account.5 In addition, the incidence ofNIDDM among Africans, Mexicans, PuertoRicans, Koreans, Japanese, Chinese, and Fili-pinos (groups for which adequate data exist)residing in the U.S. is greater than the inci-dence in their respective countries of origin.5

A widely accepted explanation for these ob-servations is genetic “thriftiness,” or a preva-lence of genotypes which are adapted to spo-radic wild food supplies and heavy physical



labor.3,86,87 As a group, Caucasians have mostlikely spent the longest time on an agriculturaldiet, and do tend to metabolize alcohol,88 dairyproducts,15,89 wheat and other glutinousgrains,90,91 and evidently sugars 5 better thanother groups.(footnote b) Under equivalent dietaryand environmental conditions, these adapta-tions may afford some protection fromNIDDM, but are certainly not a panacea.

Native Americans are considered tohave descended from a small group of indi-viduals who crossed the Bering Land Bridgebetween 11,000 and 14,000 yearsago.92-94,(footnote c) American Indians, regardlessof where they live in the Americas, have morein common genetically with high-latitude Es-kimo hunters than they do Caucasian Ameri-cans. Native Americans have also tended toremain in closed tribal societies, and manywere still hunter-gatherers 100 years ago, thusmodern agriculture, processed foods, and al-cohol have been especially detrimental to theirhealth.43 Hispanics have mixed Caucasian andNative Latin American ancestry, and have anincidence of NIDDM between these twogroups.5 In the Western quest to “eat as muchas you want and not gain weight” it is oftenforgotten that the evolutionary purpose forovereating is to gain weight, and to a greateror lesser degree, we are all adapted to do so,or we would never have survived in the past.Our ancestors gained weight voluntarily andlost it involuntarily, the exact opposite of whatmany of us attempt to do today.

In summary, both the quantity and typeof fat ingested influence insulin sensitivity.Since skeletal muscle is the largest sink for

glucose disposal, maintaining a high lean/fattissue ratio is an overall recommendation forNIDDM prevention and management. In ad-dition, reducing SFA and n-6 PUFA, whileincreasing n-3 PUFA is recommended. At leastsome n-3 should be from n-3 LC-PUFA, sincethere is variation in PUFA intake and metabo-lism among populations, and some groups withhigh NIDDM incidence appear to have a di-minished capability to convert 18-carbonPUFA to LC-PUFA.

Chromium NutritionChromium (Cr) deficiency is a caus-

ative factor for NIDDM, producing symptomsincluding fasting hyperglycemia, impaired glu-cose tolerance, decreased insulin binding andreceptor number, decreased HDL, and in-creased total cholesterol and triglycerides.52,95

A diet high in refined grains and sugars exac-erbates Cr depletion. Firstly, these foods con-tain low amounts of Cr, yet Cr is necessary tometabolize them. Secondly, a high consump-tion of sugars and insulinogenic foods in-creases Cr urinary excretion by 10–300%.96,97

Typical Western diets require more Cr thanthey provide, thus leading to long-term deple-tion of body Cr reserves. It is estimated themajority of the U.S. population does not ob-tain the Estimated Safe and Adequate DailyDietary Intake (ESADDI) of 50–200 mcg/dayCr. Similar results have been observed inCanada, the UK, and Finland.52,102,103

In rats, Cr is stored mainly in the kid-ney, and to an order of magnitude less the liver,spleen, lungs, and heart. Plasma Cr is not inequilibrium with tissue stores.104 Tissue storesare depleted by inadequate intake or absorp-tion, pregnancy, strenuous exercise, a high in-take of refined carbohydrates and processedfoods, increasing age, infections, andtrauma.52,95 Exercise increases the metabolicrate; insulin receptors in the muscle cells areactivated and glucose uptake is greatly en-hanced over basal levels. This uptake requires

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b In addition, regular alcohol consumption and chronic gas-trointestinal inflammation, such as occurs in delayed-onsetfood allergies (common for wheat and some other grains, eggs,and dairy products), are associated with decreased desaturaseactivities, and impaired absorption and metabolism of PUFA,which may further exacerbate membrane abnormalities andincrease the risk for NIDDM.65, 98-100

c Recently, the scanty evidence for entry prior to 50,000years,25, 94, 101 most of which comes from a site at Monte Verde,Chile, was officially acknowledged by thepaleoanthropological community at large.



concomitant action by Cr; however, it does notappear that Cr is efficiently recycled by thebody. Urinary chromium excretion increasessignificantly following exercise.105 Increasedcirculating insulin increases Cr urinarylosses,97 but also increases the body’s require-ments for Cr. Without Cr supplementation ordietary changes, hyperinsulinemia and glucosetolerance get progressively worse with time,and can eventually result in NIDDM.103

Chromium Absorption andAvailability: Past and Present

Brewer’s yeast, beer, whole grains,cheese, liver, and meat can be good dietarysources of Cr; however, Cr content of foodsvaries widely, and much of what is measuredmay be contamination from stainless steel pro-cessing equipment. Refining of grains and sug-ars, and processing of foods removes most ofthe absorbable Cr.95,102 Unlike most essentialtrace elements, Cr has not been shown to beessential for major agricultural plants,106,107

thus Cr levels depend simply on how andwhere various plants are grown. Accordingly,fruits, vegetables, grains, and legumes intrin-sically contain varying amounts of Cr. Soilswith abundant Cr must of necessity developfrom underlying rocks rich in Cr.

It is a fundamental principle ofgeochemistry that rocks rich in Cr (footnote d) arecommon in the Earth’s mantle and to a lesserextent in the oceanic crust, but are rare in thecontinental crust.108-110 Cr-rich rocks found onthe continents are restricted to exposed areasin which pieces of oceanic crust and/or mantle

have been pushed up onto the continents. Thistype of activity is observed only at geologi-cally active plate margins where one plate isthrust beneath another (known as subductionzones), or where plates have rifted and newoceanic crust is being created. Currently, theseactive plate margins are found along oceancoastlines, thus Cr-rich rocks are confined toareas which are now or were once geologi-cally active coasts or ocean basins. The Peru-Chile subduction trench and associated Andesmountains along the west coast of SouthAmerica is a current example of such a coast.The Great Valley of California is explainedgeologically as having been a subductiontrench circa 65 million years ago.111 Its fertile,Cr-rich 112 soil is the legacy we have today.

In humans, Cr absorption is regulatedand inversely related to dietary intake at lev-els <40 mg. Above 40 mg, absorption appearsto remain constant. Inorganic forms of Cr arevery poorly absorbed (<1%). Organic Cr com-plexes have better absorption than inorganicsalts, but the levels of absorption are still be-low 10%.104 The biologically active form ofCr appears to be a nicotinic acid-amino acidcomplex, and Cr is not effective if nicotinicacid is deficient.114 This does not mean, how-ever, that Cr nicotinic acid complexes are thenecessary or preferred type of Cr nutritionalsupplementation; on the contrary they appearto be more poorly absorbed than Cr picolinateor chromium-rich yeast extracts.104,115

Broadhurst et al115 showed that in Cr“polynicotinate” Cr is not bonded to nicotinicacid, but rather to OH and/or H

2O in an olate

structure. Further, the amount of nicotinic acidin a typical 200 mg Cr supplement is quanti-tatively insignificant with respect to the RDAof 18 mg, and especially with respect to theapproximately 100 mg necessary to reverseniacin deficiency. Cr and nicotinic acid supple-ments administered independently have beenshown to improve glucose tolerance while ei-ther component alone was ineffective.114

d This applies to cobalt, nickel, and platinum group elementsas well. The richest deposits by far of all these metals arefound in unusual deposits where ancient (1–3.8 billion year-old) mantle-derived rocks have been exposed by deep ero-sion, but not destroyed by more recent geologic activity. Themineral deposits of South Africa are the best example of this.113

The Earth was much hotter then, and plate tectonic cycleswhich may have been present must have differed consider-ably from that of the past billion years. Hence, there are nocomparatively recent examples of such high-concentrationmetal ores.



Appropriate dietary choices andsupplementation of Cr on the order of 200–400 mcg/day may help prevent NIDDM, butmay not be sufficient to reverse existing dia-betes. A recent double-blind study on threegroups of 60 Chinese Type II diabetics foundthat 500 mcg Cr (as chromium picolinate)given twice per day for four months wasgreatly superior to placebo at lowering fast-ing glucose (129 mg/dL versus 160 mg/dL),2-hr postprandial glucose tolerance (190 mg/dL versus 223 mg/dL) and nearly normalizingglycosylated hemoglobin (6.6±0.1% versus8.5±0.2%). Plasma total cholesterol and cir-culating insulin also dropped. A third groupgiven 100 mcg twice per day showed lesserbut significant improvements in glycosylatedhemoglobin and insulin levels, but not bloodglucose.116

If Cr is so poorly absorbed and spo-radically distributed, it is reasonable to askhow humans could have existed in the pastwithout developing Cr deficiencies. Perhapsmany did — we can never know for sure, butour ancestors had two points on their side.Firstly, their Cr needs were almost certainlylower because they consumed no cereal grainsor refined sugars, but did consume lean free-living game, fish etc., more balanced PUFA,soluble fiber, and wild vegetation (discussionfollows). In addition, ethnographic observa-tions show that traditional hunters make a pointto consume the brains, organs, and bone mar-row of game and fish,35,45,117,118 which are richsources of many trace elements, Cr included.104

We have no reason to think this was differentin the past: archaeological investigations ofPaleolithic scavenging/kill sites reveal effi-cient butchering techniques and evidence ofskull and bone crushing.93,117,119,120 In fact, afeature of the U.S. diet is its almost exclusivereliance on muscle meats.

Secondly, based on a continuousrecord of hominid fossils,26,32 our earliest an-cestors lived in the East African Rift Valley

for over for 4 million years, and the Rift Val-ley is an environment with abundant Cr in therocks and soils. Soils and rocks in the RiftValley are relatively rich in all trace mineralsdue the constant geologic activity.121 The Af-rican Rift, the Red Sea, and the Gulf of Adentogether form our only current example ofwhat is termed geologically a “failed ocean.”Extensive geologic investigation has con-cluded that starting 30 million years ago, theArabian peninsula moved slightly away fromAfrica, but has now nearly stopped.122 Even anovice observer can gain an understanding ofthe plate tectonics of the Arabian peninsula andthe East African Rift Valley by simple exami-nation of a map or aerial photograph of thearea. Throughout the evolution of hominids,volcanoes erupted constantly, covering the areawith trace-element rich lava and ash.121,123

Enormous lakes filled the linked fault basinswhich collectively form the Rift axis. Theselakes are in fact “proto-oceans”, in terms oftheir size, geologic origin, and very high lev-els of dissolved minerals.31

The weight of evidence fromarchaeology, hominid phylogeny, andmitochondrial DNA studies points to a singlespeciation event circa 100,000–300,000 yearsago in Africa which produced Homo sapiens.26,27,31,124,125 (footnote e) H. sapiens populations thenmigrated out of Africa to the rest of the world,rather than independent coevolution ofseparate populations of precursor H. sapiensspecies. After migration, a number ofnutritional, social, and economic factorsconfined most of the human population tocoastal environments, and in fact the majorityof the world’s population is still confined tothe coast .9,30 Adoption of agriculture, as wellas large-scale migration into interior areas, arethought to be recent phenomena, linked to the

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e In addition, a very young date of 27-53 kyr for H. erectus inJava was recently reported.129 If confirmed, this would re-quire coexistence of H. erectus, H. neanderthalensis, and H.sapiens ,and would preclude independent evolution of dis-parate H. erectus populations into H. sapiens.



recession of continental glaciers 10,000 yearsago (i.e., the end of the most recent IceAge).37,88,90 Coastal areas are generally richerin all trace elements, especially Cr, Se, and I— the three trace elements that mammals needbut plants do not.

In summary, both Cr and PUFA defi-ciencies and/or metabolic abnormalities in-crease with increasing %en from fat, intake ofrefined and processed foods, and age. Likebalanced PUFA intakes, Cr improves insulinaction and plasma lipid profiles; however, theexact mechanisms are not elucidated. Nutri-tional and geologic/evolutionary factors haveseemingly conspired to produce widespreadCr deficiencies. Therefore, supplementation ofCr well above ESADDI levels may be neces-sary to both treat and prevent NIDDM.

Very recent research has shown that Crsupplementation can improve insulin resis-tance induced in rats by feeding a high fatdiet. .126 It is plausible there is a specific rela-tionship between the actions of PUFA and Crwith respect to plasma membranes; in anycase, supplementation with both Cr and n-3PUFA may provide synergistic benefits on glu-cose metabolism and serum lipid profiles.

Phytochemical InfluencesPharmacologically active plant

phytochemicals include flavonoids, saponins,lignans, and tannins. Many of these com-pounds are bitter or astringent; therefore hor-ticulturists have selectively bred these com-pounds down to low levels, or concentratedthem in peels, which are often not con-sumed.40,127,128 Produce is consistently bred tobe larger, sweeter, and milder. The fruit andvegetables our Paleolithic ancestors ate weremore akin to chickweed, choke cherries, andkumquats than iceberg lettuce, bing cherries,or navel oranges. Consequently, we may havelost a good deal of phytochemical protectionfrom many pathologies, NIDDM included.The more bland and processed the diet, thegreater the loss. The strong-tasting vegetablekale, for example, had the highest antioxidantcapacity of 21 vegetables studied,130 which isnot surprising since wild kale is the precursorto all Brassica species, from kolrhabi to cab-bage to cauliflower. Kale bears the most simi-larity to the Brassicas we evolved eating.

Evolutionary perspectives aside, mostof us are not going to return to a diet of thebitter, fibrous, “edible weeds,” the wild pre-cursors to modern cultivated produce. How-ever, many of the aforementioned bitter andastringent phytochemicals are present todayin herbal products. The use of medicinal plantsfor diabetes is not just a search for safer alter-natives to pharmaceuticals which transientlylower blood glucose. Rather, we gain insightinto the validity of traditional tonic andadaptogenic herbs and foods. Herbal products

Figure 2. Inhibition of production of reactive oxygen species in platelets by methlyl- hydroxy chalcone polymer (MHCP).

0 2 4 6 8 10 12

100

80

60

40

20

0

INC

RE

AS

E IN

FLO

UR

ES

CE

NC

E

TIME

- No Extract Added

- 5uL 2A

- 5uL 1

Whole blood is incubated with 10 uM 2’7'- dichlorodihydrofluoresceindiacetate for 10 min, followed by a 5 min exposure to MHCP solution orvehicle control. Collagen at 20 uglmi is added, and platelets in the samplesare monitored for increases in fluorescence by flow cytometry at timesindicated. Platelets are known to produce hydrogen peroxide, particularlywhen collagen is used to stimulate them. MHCP 1 is 1 mg/mi, and is likelyto be a slightly lower molecular weight than MHCP 2A (4.5 mg/mi). Thedata show a significant, dose-dependent decrease in fluorescence withMCHP treatment.



can return valuable components to the diet,thereby making it more similar to our evolu-tionary diet with minimal effort.

According to Marles andFarnsworth,131 1,123 plants have been used totreat diabetes. Of 295 traditionally used plantsscreened in vitro, 81% were potentially antidia-betic. Over 200 pure phytochemicals areknown to be hypoglycemic. However, Marlesand Farnsworth131 caution that 1/3 to 2/3 ofthe 1,123 plants may be dangerous, andmany of the phytochemicals are hy-poglycemic due to metabolic or hepatictoxicity. Conversely, there are hypogly-cemic plants which are safe and effec-tive precisely because they help returnus to our evolutionary diet. The follow-ing subsections discuss plants whichhave clinical studies confirming effi-cacy.

Actions of PhytochemicalsIn some cases, plant

phytochemicals can directly stimulateinsulin secretion and/or action, and im-prove insulin action and binding. Com-mon spices such as cinnamon, cloves,and bay leaf have demonstrated insulinpotentiating action in vitro .132 It wasthought that these spices might havehigh Cr concentrations, but measure-ments showed no correlation betweenCr content and insulin activity. Cinna-mon was particularly active, so we fo-cused on it. From an extract of com-mercial cinnamon, a novelmethylhydroxy chalcone polymer(MHCP) was identified which increasesglucose metabolism of the cells 20-foldin vitro in the epididymal fat cellassay .128 Over 40 plant extracts havebeen investigated in this assay, includ-ing many mentioned herein; however, nonehave shown activity near that of cinnamon (R.A. Anderson, C. L. Broadhurst, M. M.Polansky, in preparation).

Botanicals demonstrating in vivo hy-poglycemic activity in animals include juni-per berries,133 izui,134 Siberian ginseng,ganoderma mushroom,135 cumin, cucumber,and bottle gourd.136 Table 1 lists some of themore promising hypoglycemic plants whichhave not yet been adequately clinically tested.

Since insulin action has been positivelycorrelated with skeletal muscle capillary den-sity,73 phytochemicals which can improve skel-

etal muscle capillary function have the poten-tial to directly improve insulin action. Ex-amples of herbal products which have beenshown to improve capillary function are horse

Common Name

ClovesCinnamonTurmericBay leafBlack walnutJuniper berriesIzuiSyrian Christ thorneGuduchiCuminBlack cuminCucumberBottle gourdGoat’s rueGanoderma mushroomJava plumSiberian ginsengCorianderSage

Latin Binomial

Syzygium aromaticumCinnamomum spp.Curcuma longaa

Laurus nobilisJuglans regiaJuniperus communisPolygonatum officinaleZizyphus spina-christiTinospora cordifolia, T. crispaCuminum cyminumNigella sativaCucumus sativaCurcubita ficifoliaGalega officinalisb

Ganoderma lucidumSyzygium jambolanumEleutherococcus senticosusCoriandrum sativumSalvia spp.

Table 1. Promising botanical treatments for NIDDM, based on in vitro or in vivo animal studies. References cited, or can be found in Bailey and Day (1989), Marles and Farnsworth (1994), Broadhurst (1997), or Duke et al. (1997).

a. Based mainly on antioxidant properties.b. G. officinalis has been tested in humans and can be effective, but is not considered generally safe. It contains the guanadine derivative galegin, which is similar to synthetic pharmaceutical hypoglycemic biguanides

Diabetes



chestnut, bilberry, ginkgo, Centella asiatica,and various standardized anthocyanin prepa-rations.40,137-139 Bilberry in particular has beenshown to improve edema and microangiopathyin diabetics.138,140

Modest buckwheat, butcher’s broom,and hydroxyethyl rutoside supplementationsignificantly regressed diabetic retinopathy inhumans, probably due to improved local cir-culation in the retina.141 These three treatmentsalso lowered total cholesterol and triglycerides,and raised HDL cholesterol. Cinnamon alsocontains procyanidin dimers and oligomers ofthe type thought to improve capillary func-tion.142

Botanical antioxidants can play a rolein NIDDM, helping maintain the integrity ofcell membranes by preventing PUFAperoxidation. As discussed above, membraneunsaturation correlates positively with insulinfunction. Many botanical antioxidants (e.g.,cloves, cumin, cinnamon, curcumin, rosemary,many mint family plants, and various biofla-vonoid preparations40,143) are both powerful andsynergistic with antioxidant vitamins. Lipidperoxidation and damage by reactive oxygenspecies are also major problems in terms ofdiabetic complications. The MHCP extractfrom cinnamon strongly inhibits the formationof reactive oxygen species in collagen-acti-vated platelets in vitro (Fig. 2), so may pro-vide synergistic benefits. In addition, somephytochemicals directly influence the PUFAdesaturase system and arachidonic acid me-tabolism.40,128,144

Traditional Tonic Plants: Humanstudies

Four traditional plants have clinicalstudies which document their efficacy:1. Bitter melon (Momordica charantia). Un-ripe bitter melon is used traditionally in India,Africa, and Asia as a diabetic remedy and bit-ter tonic food. Bitter melon contains anonpurified mix of hypoglycemic compounds

(“charatin”), and an insulin-like protein. Theeffects of bitter melon are gradual and cumu-lative, and a juice or decoction is more effec-tive than the powdered dried preparation.145

Srivastava et al145 gave 6 Type II diabetics 100ml/day of a bitter melon decoction. After threeweeks, their fasting blood glucose dropped by54%. After seven weeks, all six were at or nearthe normal glucose limit, urinary sugar wasno longer detectable, and glycosylated hemo-globin dropped nearly 2 mg%.2. Gurmar (Gymnema sylvestre). The leavesof this climbing vine are an ancient Ayurvedictreatment for diabetes.146 Gurmar appears tostimulate insulin secretion and lower choles-terol and triglycerides without side-ef-fects.147,148 In an open study, 22 NIDDM pa-tients on oral antihyperglycemics were given400 mg/day of a standardized extract for 18–20 months. All 22 were able to reduce theirmedication, and five were able to discontinueit. The extract was judged superior to prescrip-tion medication for long-term blood glucosestabilization, lowering of triglycerides, and theoverall well-being of the patients.149,(footnote f)

3. Korean ginseng (Panax ginseng). Tradi-tional Chinese medicine recognized that gin-seng helped diabetes centuries ago. Sotaniemiet al150 found 200 mg/day ginseng for eightweeks improved mood and physical activity,and lowered fasting blood glucose,glycosylated hemoglobin, and body weightcompared to placebo. This dose is exceedinglymoderate, and could be safely increased.4. Onions and Garlic (Allium cepa, Alliumsativum). Onions and garlic have been used inmany cultures to treat diabetes, but are prob-ably best utilized as adjuncts to other herbaland nutritional treatments. Onions and garlicboth contain disulfide-bonded thiosulfinatesand diallyldisulfides. Insulin has a similar dis-ulfide bond, so Allium disulfide chemicals are

f Since gurmar appears to act primarily by stimulating insulinsecretion, it may not be appropriate for chronichyperinsulinemia.



thought to compete with insulin for endog-enous insulin-inactivating compounds. A verylarge dose of 10 gm/kg onion or garlic extractlowered fasting blood glucose and improvedglucose tolerance by 7–18%.135

A review by Koch and Lawson151

found lower doses of garlic are effective; how-ever, most of the studies cited are older anduncontrolled. Newer studies indicate the sul-fur-containing phytochemical s-allycysteinesulfoxide (alliin) may indeed be important forgarlic to be effective. Garlic and onion lipidfractions (about 1-3% by weight) contain themajority of this phytochemical. In an openstudy, a single dose of 125 mg/kg onion oillowered fasting glucose in six subjects from75 to 59 mg/dl, while those receiving placebowent from 72 to 66.5 mg/dl. In this study, pla-cebo also significantly reduced blood glucose,and the dosage translates to 12.5 g onion oilfor a 100 kg human, so it may not represent arealistic clinical approach. In a double-blindstudy of 20 subjects, 800 mg/day garlic stan-dardized for alliin (dose not specified) wasgiven for four weeks. The 10 receiving garlicsignificantly lowered their fasting blood glu-cose from 90.6 to 77.8 mg/dl, while 10 receiv-ing placebo went from 88.6 to 85.8 mg/dl, anonsignificant change. In another study, spraydried garlic powder (which does not containalliin) was given at 700 mg/day for a month,and had no effect.

Beyond FiberHigh fiber diets are uniformly

recommended for diabetics.14 Particularlyimportant is soluble fiber, found mainly infruits, vegetables, and some seeds. Insolublefiber is more characteristic of brans and husksof whole grains, nuts, and seeds. Soluble fibersinclude pectins, gums, and mucilages, whichact to increase the viscosity of food in theintestine, thus slowing or reducing theabsorption of glucose. In this respect, any dietfeaturing large quantities of raw or lightly

processed vegetables is beneficial. Ourevolutionary diet was unprocessed and oftenrich in fresh vegetation and soluble fiber;however, today many shun vegetables rich insoluble fiber such as okra, turnips, andparsnips. Herbs and foods with high levels ofpectin or mucilage have been used successfullyfor diabetes, and as discussed below, thesoluble fiber is effective. However, some ofthese botanicals provide synergistic benefitsbeyond the physical effect of inhibitingglucose absorption.

1. Flax seed (Linum usitatissimum).Flax seed meal is one of the richest sources ofsoluble and insoluble fiber known. Cunnaneet al152 administered 50 g glucose along withplain water, or water containing mucilage ex-tracted from flax seed to four nondiabetic sub-jects. The flaxseed mucilage dose decreasedthe area under the glucose tolerance curve by27% compared to water. Six others were given50 g white bread or bread with 25 wt% flaxmeal. The flaxseed bread decreased the areaunder the glucose tolerance curve by 28%compared to plain bread. Since the mucilagecontent of flaxseed meal is only a few per-cent, the effect is greater than can be accountedfor by simple inhibition of glucose absorption.Flax seed is the richest food source oflignans153,(footnote g) and is also rich in protein,PUFA, and minerals,154,155,(footnote h) all of whichmay be beneficial.

2. Fenugreek (Trigonella foenum-graecum). Fenugreek is another Ayurvedic tra-dition proven effective. Whole fenugreek seedsare about 50% fiber, with 20% of that muci-lage. In a double-blind study, 10 Type I dia-betics were given meals with 100 g/dayfenugreek powder (ground defatted,

Diabetes

g Thompson et al153 report 52,675 mg/gm lignan excretionfrom ingesting whole flax seed; 67, 541 mg/gm from flaxmeal; the next closest source is legumes with 201-1287 mg/gm.h Especially K, Mn, Cu, Zn, Ca. Flaxseed contains 5600-9200mg/kg K on a dry weight basis, more than any other foodsource.154



debitterized seeds) or regular meals. After 10days, fasting glucose decreased by 30%, andglucose tolerance improved in the fenugreekgroup. Sugar excretion dropped an astonish-ing 54%, yet there was no increase in insulinlevels.156 Since fasting glucose was stronglyaffected, simple inhibition cannot be the onlyexplanation. In addition to mucilage,fenugreek also contains protein, saponins, andthe hypoglycemic phytochemicals coumarin,fenugreekine, nicotinic acid, phytic acid,scopoletin, and trigonelline.40,131 In otherdouble-blind studies, 15–25 g fenugreek pow-der were similarly effective for Type II dia-betics.157 In all studies, fenugreek was very ef-fective at lowering LDL cholesterol and trig-lycerides.

3. Nopal (Opuntia spp.). Widely usedthroughout Latin America, nopal (prickly pearcactus), is rich in pectin. Nopal is a traditionalfood of Native Southwestern hunter-gather-ers.43 Frati et al158 gave eight fasting diabetics500 g nopal. Five tests were performed on eachsubject, four with different cooked or raw cac-tus preparations and one with water. After 180minutes, fasting glucose was lowered 22-25%by nopal preparations, as compared to 6% bywater. In a rabbit study, nopal improved toler-ance of injected glucose by 33% (180 minutevalue for comparison) as compared to water.136

In both these cases there was no glucose inthe intestines. A purified extract of Opuntiafuliginosa given at 1 mg/kg/day for eightweeks along with insulin normalized bloodglucose in diabetic rats. For the followingseven weeks the O. fuliginosa extract wasgiven alone, and glycemic control was main-tained. O. fuliginosa, but not insulin, also nor-malized glycosylated hemoglobin levels;clearly, these results preclude a predominantrole for the “fiber effect” alone.159 The nopalresearchers concur that although the cookedand raw cactus were effective, preparationsfrom commercially dehydrated nopal are noteffective. In addition, not all species of Opun-tia are similarly effective.

4. Ivy gourd (Coccinia indica). In adouble-blind study of 32 diabetics, six tabletsof ivy gourd leaves per day for six weeks de-creased fasting glucose and improved glucosetolerance by 20%.160 Although ivy gourd inrich in pectin, it also helps inhibit gluconeo-genesis and stimulate glucose oxidation.

Other plants which may have the an-tidiabetic “soluble fiber plus” synergy are aloevera, Indian cluster bean, and carrots, and thereare doubtless more to be discovered and clini-cally tested. In summary, every effort shouldbe made to encourage diabetic individuals toincrease produce consumption; however, ifcompliance is a problem, similar benefits canbe obtained with quantitatively lesser amountsof particular botanicals. There is good evidencethat many botanicals have benefits for control-ling diabetes that act on the cellular metaboliclevel, going far beyond the simple inhibitionof glucose absorption.

Summary And RecommendationsHuman nutritional needs are strongly

dictated by Paleolithic hunter-gatherer needsand lifestyles. As far as Homo sapiens is con-cerned, agriculture is a new experience. “Ge-netic susceptibility” to NIDDM may be uni-versal in H. sapiens, and the degree to whichthe disease progresses is potentially due to 1)the degree to which the diet strays from theevolutionary food types; 2) the degree to whichthe diet strays from the evolutionary micro-nutrient and triglyceride balance; 3) variablegene expression resulting from (1) and (2).Ethnic minority populations adopting Westerndietary habits are particularly prone toNIDDM.

Nutritional intervention is required inorder to prevent the initiation of insulin resis-tance and glucose intolerance which canprogress to NIDDM. Maintaining a high lean/fat body mass ratio and regular exercise are ofcritical importance. Consuming foods moreclosely aligned with a hunter-gatherer diet can



reduce obesity and provide glycemic controlin many individuals. Both individuals and eth-nic groups vary in their ability to metabolizegrains, dairy products, and alcohol. Consum-ing dietary carbohydrates from fresh vegetableand fruit sources, which was the only optionnormally available to our ancestors, is recom-mended due to the synergistic benefits of fi-ber, phytochemicals, and a low density of car-bohydrate per unit food weight. Those whodo not choose to eat adequate produce can ben-efit from a number of herbal dietary supple-ments, which provide not only soluble fiber,but also phytochemicals which directly influ-ence glucose metabolism.

Both the quantity and type of fat in-gested greatly influence insulin sensitivity. Re-ducing total fat, SFA, n-6 PUFA, and increas-ing n-3 PUFA is generally recommended; how-ever, there is evidence for variation in PUFAintake and metabolism throughout the popu-lation. Some ethnic groups with high NIDDMincidence may not convert PUFA to LC-PUFAas efficiently as other groups. A good rule ofthumb is to supplement PUFA in a 1:1 n-6 ton-3 ratio, since Western diets are typically“front-loaded” with n-6 PUFA. A combinationof LA, LNA (18-carbon PUFA) and LC-PUFAmaximizes benefits while minimizing risks.

Chromium supplementation at 200-400 mcg/day might be preventive for NIDDM;however, dosages at or above 1000 mcg/daymight be required to reverse or improve exist-ing diabetic symptoms. Typical Western dietshigh in fat, grain products, and sugars notsupplemented with Cr might not afford pro-tection from NIDDM, regardless of the degreeto which the foods are refined; however, de-velopment of glucose intolerance will be has-tened when foods are highly refined.

AcknowledgmentsThe support of Drs. Richard A. Ander-

son (Human Nutrition Research Center) andWalter F. Schmidt (NMR Laboratory), and

associates, at the USDA Beltsville, MD ARS,and that of Dr. James A. Duke, USDA ret. andHerbal Vineyard Inc. is gratefully acknowl-edged.

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