Ward Dean, M.D. is one of the most prominent anti-aging physicians in the world today. Apart from his groundbreaking work with Professor Vladimir Dilman, in forming the; 'Neuroendocrine Theory of Aging and Degenerative Disease' he is also a world renowned expert in Biological Aging Measurement and has published what is widely considered to be the definative work on the subject. Dr. Dean is the Medical Director for Vitamin Research Products in Carson City, Nevada, the Medical Director of Inner-Age, and is also Medical Doctor to the Watson Health Center, Milton in Florida.

AAM: Dr. Dean, thank you for taking the time to discuss the Neuroendocrine Theory of Aging and the biguanide drug Metformin.

Dr. Dean: as you know, since the early '90s, I've been recommending Metformin as the most effective anti-aging drug there is. I think it still holds that distinction. In fact, the Life Extension Foundation recently made that same claim on the cover of their magazine.

You were kind enough in Spring 2000 to provide the IAS Anti-Aging Bulletin with an an article about Metformin outlining its success in assisting weight loss. For the benefit of our readers, would you please explain the purpose of Metformin, at least from the 'official approved-use' perspective?

Sure...Metformin or Glucophage is approved for diabetes. Specifically, Type II 'maturity onset' diabetes. Metformin has an action mechanism that is completely different from the older antidiabetic drugs, like the sulfonylureas. The sulfonylureas act to stimulate the release of insulin from the pancreas. The problem is, Type II diabetics are insulin resistant, and already have too much insulin. So although the sulfonylureas lower blood sugar by elevating insulin levels, they actually make the condition worse by causing further insulin resistance. Metformin acts by restoring insulin receptor sensitivity, not only in the muscles, but also in the hypothalamus, the central regulator in the brain. Although Metformin was originally approved for Type II diabetics only, I’ve routinely used it on my Type I, ‘insulin dependant’ diabetics. Despite Type I diabetics producing insufficient quantities of insulin, they, like the Type II diabetics, are insulin resistant. Consequently, I recommend that Type I diabetics use Metformin along with their insulin. This way, they can get away with less insulin, and the Metformin greatly reduces the wild swings in blood sugar that most insulin dependant diabetics suffer from. In addition, Metformin is widely recognized as the drug of choice for the polycystic ovary syndrome (PCOS). It works equally well for any woman with ovarian cysts.

So how does the act of restoring insulin receptor sensitivity aid in the control of aging?

As we age, we are all becoming diabetic, and some of us are just more diabetic than others. I consider Metformin to be a 'metabolic rejuvenator'. It actually restores the individual’s capacity to metabolise carbohydrates. In addition to normalizing blood sugar and insulin, it lowers cortisol, helps to normalize blood pressure, lowers cholesterol and triglycerides, stimulates the release of growth hormone, and enhances the immune system.

Overall Metformin looks like a rather remarkable substance, beneficial for weight control, lowering cholesterol ratios and possibly even extending life span. What potential side effects and contraindications have you noted with your patients?

The only side effect I have witnessed in about 10% of my patients is stomach upset and diarrhoea. I've found, however, that almost everyone can build up a tolerance to it. I suggest that my patients start with a low dose, as little as one, or even a half tablet per day for a week or two, and then gradually increase the dose as they develop a tolerance. There is a theoretical problem of lactic acidosis in patients with impaired kidney function, but in practice, I have never seen this, despite monitoring thousands of patients on Metformin. Nevertheless, I believe that anyone with impaired kidney function should take Metformin only under the care of a physician, and should have their blood levels of lactic acid checked periodically.

What dosages do you normally prescribe?

I routinely recommend 1500 mg per day and can recommend as much as 2,000 mg per day, however I don't see much benefit in increasing the dose beyond that level. If a patient is not able to tolerate high does without gastric upset, I suggest they take whatever dose they can tolerate.

Are there any additional substances that can be used synergistically along with Metformin?

Metformin has been shown to impair the absorption of vitamin B12, so it is probably prudent to make sure that you’re taking plenty of B12. I don’t have to tell my patients that, of course, as they’re usually already taking plenty of vitamins. Metformin has also been shown to raise homocysteine, so extra folic acid and Vitamin B6 should also be taken. If homocysteine levels are elevated, I recommend adding Anhydrous Betain (Trimethylglycine) in a dose of about 6-9 grams per day. If a patient is diabetic, or a starch junkie, the starch blocker Acarbose (Glucobay) can also be used. If the patient is a diabetic, I would add Actos or Avandia to the Metformin. These are also insulin receptor sensitizing drugs which can enhance the glucose-lowering efficacy of Metformin by up to about 30%.

You wrote an interesting article about Acarbose in the Fall 2000 IAS Anti-Aging Bulletin, discussing how it blocks the update of starches, as well as its ability to enhance weight loss. Off hand, are you aware of any patients who have experienced the benefits of this type of therapy and approach?

Metformin is a real life-changing drug for many people. In addition to being one of the most effective weight loss drugs there is, it has the effect of making people feel better. The three things I keep hearing over and over from my patients on Metformin are: 'I feel better; I've got more energy; and I've lost my carbohydrate cravings.'

This whole area of anti-aging treatment is clearly very effective. We know of course that the accumulation of Advanced Glycated End products, or AGEs, is much greater in diabetics compared to non-diabetics, and that diabetes has often been viewed as a form of accelerated aging. I suspect that even more focus will be placed on what Dr. Raven called Syndrome X, what is your view Dr. Dean?

Professor Vladimir Dilman is the originator of the Neuroendocrine Theory of Aging. Dilman preceded Reaven by more than ten years, and his concepts went far beyond Reaven’s. Syndrome X is a pattern of hyperinsulinemia, hypertension, and coronary artery disease. Dilman, however, described the ‘metabolic pattern of aging,’ which not only includes the elements of ‘Syndrome X,’ but also incorporates other metabolic changes as well, which are a part of all the other chronic degenerative diseases. The lynchpin in all of these conditions, is hyperinsulinemia, and the loss of hormone receptor sensitivity. I updated Dilman’s work in our 1992 book, ‘The Neuroendocrine Theory of Aging and Degenerative Disease’ [Ed.- unfortunately, out of print], and in a series of articles for the Vitamin Research Newsletter, all of which are available in the anti-aging section on my website at www.warddeanmd.com. Hyperinsulinemia is involved in Syndrome X and the Metabolic Pattern of Aging. Since Metformin normalizes insulin, blood sugar, and a number of other age-related parameters, it really is a true anti-aging, life extending drug.

I’ve seen your website, and it is really quite interesting, especially some of the pages that are unrelated to health and life extension, and I often recommend your site to others. Perhaps I can say in closing that we would be keen to hear from any clients out there using Metformin as to what their experiences have been, and to keep us informed of their progress. Given the fact that Metformin is readily available and inexpensive, this is an anti-aging medicine that most can afford.

I agree. I think everyone over 35 should be taking Metformin.

We welcome your input Dr. Dean and keep up the good work.

My pleasure.

Dr Dean was interviewed by Phil Micans