[ed. note: Michael Jorrin, who I like to call “Doc Gumshoe” (he’s a longtime medical writer, not a doctor) writes about health and medicine topics for us from time to time. His words and thoughts are his own.]

Let me begin with a disclaimer: I am not skinny, but neither am I fat. This chapter in the Epistles of Doc Gumshoe is neither an apologia nor a stern lecture. True, a year or so ago, at my regular medical tune-up, a nurse erroneously subtracted a full four inches from my height, and in consequences, calculated my BMI as being just over the lower boundary for obesity. This was because she was a very, very short woman, and could not see to the top of my head. When I saw that my medical record showed that I was obese, I fussed considerably, but to no avail. What was written was written.

Perhaps because of that bit of incorrect information, which has somehow leaked out into cyberspace, I am bombarded daily – nay, hourly, it seems! – with inducements to take part in sure-fire, easy-as-pie (and twice as yummy!) programs to trim my waistline and, in consequence, extend my lifeline.

Naturally, my mean-spirited nature has led me to scrutinize these, and to seek answers to two principal questions:

One, is there a possibility that some of these weight-loss schemes might work, at least a little?

Two, is it really the case that losing weight (if one is indeed overweight or obese) will add to one’s life expectancy?

Before looking at any of these in any detail, let me offer some preliminary comments:

First, in spite of the claims that many of these weight-loss schemes make to the effect that by taking their pill you won’t have to diet, I would guess that people who adopt these plans do try to be at least a tiny bit careful about what goes in through their gullets. They don’t take their daily weight-loss supplement and then proceed to feast on Turducken and Boston Cream Pie. I think they try to diet a bit in addition to taking their magic pill.

Second, it depends on the degree of obesity. At a certain point, obesity itself is a clear and present danger, and just about anything that gets rid of some avoirdupois helps alleviate the danger.

Two birds with one stone

So let’s look at some of these weight-loss plans. The first one that I took a close look at was from an outfit called BioTrust Nutrition, whose slogan (and website) is fixyourbloodsugar.com. (I seem to remember that a former presidential candidate, with credentials in the pizza business, was sending a zillion emails to all and sundry, directing them to that website. Perhaps he was trying to compensate for having fattened people up with his pizza.)

The pleasing premise of this outfit is that all weight gain is due to insulin resistance. The reasoning goes as follows: in a healthy person with normal insulin function, all blood sugar is metabolized and converted to energy, therefore none of it is converted to loathsome fat. But, with insulin resistance, the insulin receptors are unable to utilize the circulating insulin, so then the body can’t do anything with blood sugar but convert it to fat, and there you are. (That line of reasoning omits conversion of glucose to glycogen, but so what.)

On the face of it, every single denizen of Gumshoeland sees a problem with this: energy is demand, and blood sugar is supply, and if the supply exceeds the demand, what are we going to do with it? Store it, of course.

We’ll ignore that quibble and proceed with their proposal, which is put forward by a very plausible chap named Joel Marion in an interminable video, which I watched all the way through. He starts out proclaiming that there are four foolproof ways to deal with insulin resistance and lose weight.

Three blind alleys and the True Way

Way number one is exercise. Intense, weight-bearing exercise for at least one hour a day will do the trick. Unfortunately, this is not practical for most people.

Way number two is megadoses of cinnamon. Twelve 500 mg. capsules a day will do the trick – about two teaspoonsful. Unfortunately, the cinnamon you can buy at the grocery store is usually not real cinnamon – it might even be cinnamon-flavored saw dust. Also, unfortunately, most people can’t tolerate that much cinnamon.

Way number three is a really, really strict diet – no sugar and no carbohydrates. Unfortunately, most people find it difficult to subsist on kale and quinoa.

So, after the unfortunate fact that the first three foolproof ways are just unfortunately not practical, we’re left with way number four, their special nutritional supplement, BioTrust Nutrition’s IG-5, which contains no fewer than five guaranteed substances that will address insulin resistance, and consequently, take the pounds off in double digits (possibly triple digits).

So, what’s in it?

1. Cinnamonum cassia, sometimes also called Chinese or Ceylon cinnamon. Apparently (I did not know this) there are lots of kinds of cinnamon, and this is the one with allegedly medicinal properties. According to WebMD, it is “used for many conditions, but so far science has not confirmed that it is effective for any of them. Research does show that it is probably not effective in lowering blood sugar in Type 1 or Type 2 diabetes.” Among the conditions that some people use it for are impotence, high blood pressure, diarrhea, kidney disease, and bed wetting.
2. Berberine, a plant alkaloid of the isoquinoline family. Many related substances have important medicinal qualities, and berberine also has some clear medicinal qualities. For example, it is part of standard treatment for leishmaniasis, an infection caused by a protozoal parasite. It is found in a number of related plants, including European barberry, goldenseal, goldthread, Oregon grape, phellodendron (NOT philodendron), and tree turmeric. It is also taken for heart failure, applied to the skin to heal burns, and to the eye to treat trachoma. It appears to upregulate insulin receptors, and thus have some possible use in Type 2 diabetes.
3. Pterocarpus marsupium, also known as Vijayasar, the Indian King Tree. It appeared to lower blood glucose in rats with induced Type 2 diabetes. A clinical study in India found that it was similar in effectiveness in treating type 2 diabetes patients as the drug tolbutamide (Orinase), which was one of the very first oral drugs used in treating diabetes. Tolbutamide, like other sulfonylureas, boosts insulin release. It is seldom used these days, owing to side effects more severe than with other sulfonylureas, and it strikes me as an odd drug against which to evaluate the Vijayasar candidate.
4. hydroxyisoleucine, which is fenugreek, familiar to many supplement advocates. There is evidence (in animal studies) that it activates an insulin receptor, phosphoinositide 3, thus reducing insulin resistance in the liver and in muscle, and also potentiates insulin release.
5. R – alpha lipoic acid. This is the right-handed enantiomer of alpha lipoic acid, meaning that it’s chemically identical to the left-handed molecule, of which it is a mirror image; however, in many chemical reactions what’s important is the precise shape of the molecule, since the interactions are dependent on the fit of the molecule – like a key in a lock. It is a known antioxidant, and is used to treat the symptoms of diabetic nerve damage. Lipoic acid has also recently been found (by researchers at Oregon State University) to have significant effects on circadian rhythms – the physiologic changes that strongly influence our sleeping and waking cycles. Many genes are affected by circadian rhythms, and when out of balance they can play roles in cancer, heart disease, inflammation, hormonal imbalance and many other areas.

Sounds good, but will it work?

Thus, the components of IG-5 do have some potential activity in controlling insulin resistance and treating Type 2 diabetes. But, going back to the presentation by the fixyourboodsugar.com chap, is there any reason at all to suppose that taking this miraculous pill will make people lose weight without recourse to dieting? Because that’s what the presentation very strongly implies – the graphic that introduces it is a photograph of an exceedingly yummy and gooey pizza, and the presenter as good as says that trying to diet is useless – the basic message is take the pill and eat the pizza.

Granting that the ingredients in IG-5 have medicinal properties of some kind, there remain serious doubts about the efficacy and safety of this preparation.

We have no idea of what the right doses of these agents are. The effects of ingesting any substance depend greatly on the dose. At one end of the spectrum, in minuscule doses, a particular substance may not do anything at all, while at the other end it may kill you. My guess regarding the dosage of active ingredients in most supplements is that the manufacturers err on the low side. They really don’t want to poison anybody. That would not be good for business. But getting the dose right requires lots of clinical studies, and, as we know, those are expensive.

We also don’t have any idea whether taking all five of these potentially active substances together might not mean that there are dangerous interactions between them. Drug interactions are by no means uncommon; some can have quite serious consequences. For example, some antihistamines (now off the market) were metabolized and excreted via the same pathway as some common antibiotics and even some foods (e.g., grapefruit). The result was a build-up of the antihistamine concentration, to the point where it caused fatal cardiac arrhythmias. Unearthing these interactions requires diligent research beyond the capacities of most supplement manufacturers.

And, of course, they’re entirely unregulated, so we don’t really know what we’re getting. In a previous Doc Gumshoe piece (Supplements Versus Drugs: An Unfortunate and Unnecessary Feud), I cited a Canadian study (Newmaster SG et al. BMC Med. 2013; 11: 222) that found that of 44 supplements marketed by 12 different companies, only two companies sold supplements that were exactly as described on the label. Two were entirely, totally, completely bogus, consisting only of fillers, and the other 8 were greatly adulterated. There’s no way to make sure that you’re getting what you pay for – even if the supplements work.

But what about some of these other weight-loss miracles?

Every day, without fail, something pops into the inbox touting garcinia cambogia. I can hear the Gumshoe denizens sighing with fatigue. A lot of these little invitations to flatten my tummy (and my wallet) are linked to the super-celebrity Dr Mehmet Oz, of whom we will speak later. I will try to be brief regarding garcinia, and those of you who already know about it should feel free to skip forward, to a brief discussion of yet another diet miracle “endorsed” by Dr Oz.

Garcinia has many names. My favorite is “Garcinia gummi gutta,” which is the scientific name of the tree, also known as Malabar tamarind. The fruit is similar to the regular tamarind, Tamarindus indica, and sometimes also used in cooking. (I make an excellent chicken in tamarind sauce – is that why I haven’t gained weight lately?) Garcinia contains hydroxycitric acid, which supposedly messes with an enzyme called citrate lyase, which in turn interferes with fatty acid metabolism. Studies have confirmed that indeed, hydroxycitric acid does this in a test tube. But garcinia does not appear to do this (unfortunately!) in humans. As long ago as 1998 – well before Dr Oz glommed onto it as another miracle – a careful study was published in JAMA, which reported that over a 12-week period, garcinia three times a day did not result in any more weight loss than placebo. (Heymsfield SB et al, JAMA 1998 280 (18): 1596–1600)

Since then, many investigators have studied garcinia and come up with similar conclusions: taking garcinia supplements does not result in significant weight loss in humans. For example, a 2011 analysis of 12 clinical trials found that the garcinia supplements caused small reductions in weight, averaging less than a kilogram, and concluded that the clinical relevance of this effect was uncertain. (Onakpoya L et al, J Obes 2011:509308)

Does that spell doom for garcinia cambogia? By no means! Lots of us are somewhere between merely concerned and out-and-out obsessed with our weight. Practically everyone connected with health care in any way acknowledges that too many Americans are too heavy, and that this has consequences for health and for the nation’s economy. Moreover, lots of people are concerned/obsessed about their weight for reasons having to do more with appearance than with health, and that’s okay too. There’s evidence, for example, that job-seekers are better off looking slim, and that overweight folks are disadvantaged in many ways. So it’s no wonder that when word about these easy fixes is shouted from the rooftops, lots of folks are willing to give it a try, especially if it’s sold to them with the promise that they won’t have to go on strict diets or spend hours lifting weights

Another Dr Oz favorite

This one is called forskolin, another herbal extract, from the plant Coleus forskohlii. The specific mechanism is that it activates an enzyme called adenyl cyclase, which in turn increases cyclic adenosine monophosphate (cAMP). And cAMP, among other things, increases the contractility of cardiac muscle and the elasticity of the vascular system, which may have some benefit in lowering blood pressure.

That particular herbal extract has been used “since ancient times” to attempt to treat a great variety of conditions and diseases. Currently some practitioners are recommending it for diseases including asthma, allergies, skin conditions such as eczema or psoriasis, obesity, dysmenorrhea (period pains), irritable bowel syndrome, urinary tract infections, high blood pressure, angina, cancer, blood clots, insomnia, sexual problems in men, and convulsions. But, according to WebMD, there is insufficient evidence of the efficacy of forskolin in any of these conditions.

Forskolin, given intravenously, may be effective in alleviating the symptoms of some forms of congestive heart failure by reducing pulmonary vasoconstriction.

However, how forskolin’s mechanism of action includes effectiveness as a fat- burner, as Dr Oz alleges, is a mystery to me. Dr Oz engages in a little demonstration on television in which he ignites an inflammable wrapper of some sort (which goes up in a spectacular sheet of flame), revealing underneath an intact model representing our muscle structure, the implication being that forskolin burns off the fat and leaves the muscle untouched. Just what everybody wants!

Unfortunately, there’s no evidence that this actually happens. I’m not saying that some people don’t take forskolin and subsequently lose weight, but I’m guessing that these people also diet, whether they know they’re doing it or not. They’re on a personal campaign to lose weight, and they ease back on the French fries and soda pop.

… and a tiny bit more about another one …

A really tiny bit: also being hyped is something called ProBio Slim. It is identified as a “probiotic” by the manufacturer. The active ingredient is green tea extract, also known as epigallocatechin gallate, or EGCG. As with many supplements, it is used for a lot of different conditions, and may indeed have some effectiveness in some conditions, in some persons, under some circumstances. But high doses can be toxic and even deadly, and it has been associated with liver cancer. A recent study reported a case of severe hepatitis in a 63-year-old woman who had been taking high doses of a green tea extract. When she stopped taking the supplement and got treated, the condition rapidly resolved (Pillukat MH et al, J Ethnopharmacol. 2014 May 24. pii: S0378-8741(14).

The 63-year-old woman in question took the EGCG pills at the suggestion of a cancer support group. From where I sit, risking hepatitis in order to treat cancer might make sense, but risking hepatitis to lose weight makes no sense whatever. That would be (as in the case of the antihistamine that led to fatal heart arrhythmias) like risking cardiac death to treat hay fever: a thoroughly bad bet.

Dr Oz gets a slap on the wrist

The celebrated TV personality was summoned before the Senate Subcommittee on Consumer Protection, Product Safety, and Insurance, and given a dressing down. Senator Claire McCaskill, Chair of the committee, charged him with making assertions about products that have little or no scientific research to back them up. “The scientific community is almost monolithic against you in terms of the efficacy of the three products you called ‘miracles,” she said. “I don’t see why you need to say this stuff when you know it’s not true.”

The committee cited statements by Oz such as this one: “Thanks to brand new scientific research, I can tell you about a revolutionary fat buster,” which he said on his show in November, 2012. On the screen behind him were the words “No exercise. No diet. No effort.” He continued, “It’s called garcinia cambogia.”

Oz waffled a bit and ate a few mouthfuls of crow. He said that he couldn’t be held responsible for what advertisers say about the products he mentions, adding that he has already toned down the language he uses to discuss the products. “To not have the conversation at all about supplements would be a disservice to viewer,” said Oz. “In addition to exercising an abundance of caution in discussing promising research and products in the future, I look forward to working with all those present today in finding a way to deal with the problems of weight loss scams.”

Back to my two questions

To the first question, is it possible that some of these will help some people lose weight, at least a little, the answer is maybe so, with the emphasis on “at least a little.” But possibly the mechanism has more to do with the placebo effect than the actual physiologic activity of the supplement – taking the weight-loss pill encourages an attitude that results in some weight loss, but not because the pill is doing much of anything.

To the second question, will losing weight really add to your lifeline, there’s data that conflicts with the conventional wisdom that overweight and obesity is bad no matter what. It’s sometimes referred to as the “obesity paradox.” A recent study provides some detail. It is a meta-analysis of 36 studies in tens of thousands of patients with coronary artery disease who had coronary revascularization. The thinnest (BMI less than 20) had the highest death rate during the follow-up period, 1.8 to 2.7 times higher than the mean for the whole cohort. The patients with the lowest mortality were overweight (BMI 25 – 30). Obese and severely obese patients (BMI 30 – 35 and greater than 35) respectively had death rates 27% and 22% lower than patients with “normal” BMIs, 20 – 25. (Sharma A, Mayo Clin Proc 2014; DOI: 10.1016)

This should not come as a surprise to the Doc Gumshoe faithful. Back in December, I posted a piece entitled “Tidings, Mostly Glad,” and this was in it:

Unless you want to be a fashion model, it might be that being overweight (i.e., BMI > 25 to 30) is not always and without exception a Bad Thing. The old familiar Goldilocks principle applies there as well. In a study in more than 9,000 patients aged 70 to 75, the lowest death rates for cardiovascular disease, cancer, and COPD, were in individuals with a BMI of about 27.5, which precisely in the middle of the “overweight” classification. Overall, the death rates in “overweight” subjects were about 13% lower than in those with “normal” BMIs. The highest risks were in underweight subjects of both sexes, and normal weight persons had approximately the same all-cause mortality hazard ratios as those who were over the “obese” marker – BMI greater than 30.0.

This certainly doesn’t mean that we should stuff ourselves with gigantic quantities of roast goose and flaming puddings over the holidays. And we should take note that the population in which that study was conducted was somewhat elderly, and sometimes underweight oldsters are a bit frail and don’t have much resistance when they get sick. But it does tell us that we should look at those vaunted BMI numbers with a skeptical eye.

So here’s where Doc Gumshoe comes out: putting on a lot of excess weight is certainly not good, no matter at what age. There’s no doubt that becoming obese is a direct route to a number of diseases, including cardiovascular disease and diabetes. The question is, what’s the risk/benefit equation when it comes to taking off that excess weight? We all know the rate of recidivism relating to rapid weight loss – it’s followed, pretty often, by rapid weight gain. Losing weight slowly by means of “life-style changes” is proclaimed as the ideal, and it certainly does work. I know a person who lost quite a bit of weight by doing nothing more than cutting out soda pop. But I’m skeptical of a weight-loss program that relies principally on the kind of supplements that I see hyped every day. They might work a little. As to extending our lifelines, my eyebrows go way, way up.

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Keep the comments coming, whether kudos or excoriations – all are welcome! And please let me know what you’re interested in hearing about. Thanks, Michael Jorrin (aka Doc Gumshoe)