Tag Archives: Fructose

Leptin Resistance

What is Leptin?

Leptin is a hormone released by fat cells that helps regulate hunger. And it may hold the key to why a low carb / paleo diet works for so many people.

Role of Leptin in Hunger Signals
Leptin and Hunger
(Click Image to Enlarge)

Success on a low carb / paleo diet is often attributed to “never feeling hungry”, an effect not seen on other diets. People point to the satiating aspects of fat or protein in eliminating hunger, but dieters may be suffering from a rarely diagnosed condition called leptin resistance that is corrected by the low carb diet.

Leptin circulates through the bloodstream in an amount directly proportional to the amount of fat you have. In theory, the more leptin you have circulating the less you will eat, because it signals that you have enough stored energy for all your metabolic processes. When leptin levels dip, it signals the brain that you are hungry.

So, that means fat people should never be hungry, right? Not so fast, grasshopper.

Resistance is Futile

Most low carbers are familiar with the concept of insulin resistance in those with type two diabetes and metabolic syndrome. In a healthy individual, insulin signals the cells that glucose is available, and the cells respond and allow the glucose to enter the cell (if they need the energy). Insulin resistance is a condition where the cells become resistant to the effects of insulin, requiring more and more insulin to deal with blood sugar levels. If a regular cell opens the door to a gentle knock, the insulin resistant cells respond only to ferocious pounding on the door with a battering-ram’s worth of insulin. The pancreas, which produces insulin, cannot keep up with the demand for more and more insulin, and dangerously high levels of blood glucose result.

A similar thing happens with leptin resistance, but through a different mechanism. There’s no shortage of leptin in an otherwise healthy obese person, and the fat cells never grow tired of producing it. But the circulating leptin is blocked and cannot turn off the hunger signal. The fat person remains hungry. And hungry people eat.

What Causes Leptin Resistance?

Some have theorized that dietary fat and blood glucose levels interfere with leptin. While there is a link between leptin resistance and the levels of fat circulating in the blood (triglycerides), eating dietary fat doesn’t seem to have an effect. Recent evidence showing a diet high in fructose contributes to leptin resistance adds to the growing body of evidence against high levels of fructose in the diet. The amount of fat in the diet did not matter; leptin resistance peaked with the high fructose diet, and reversed itself to normal levels when the rats ate a sugar free diet, no matter how much fat they had. Lucky rats.

We know that leptin signals our brain that enough energy is present, and the body does not need any more food. Leptin is able to cross the “blood brain barrier” (BBB) to do this. The BBB is a protective system of small capillaries that protects the brain from most chemicals but allows the important ones through. It works like a filter. So what causes the curious case of leptin resistance, where this essential hormone is blocked by the BBB? As Dr. Mike Eades explains:

Research done a couple of years ago in St. Louis and in Japan pinpointed the problem. Triglycerides – fat circulating in the blood – interrupts the passage of leptin across the BBB. If trigylcerides are high, which they are in most obese people, then, basically, they block the movement of leptin into the brain. So, leptin levels are elevated in the blood, and triglycerides keep the leptin from getting to where it needs to get to shut off hunger.

One Solution

Controlling trigylceride levels can reverse leptin resistance. In my own experience, hunger evaporated on my low carb diet as my triglycerides fell from 344 to 105. Before that, I was often hungry, even after eating past the feeling of fullness and often to discomfort. On my low fat diet 15 years before, I was miserable because I was always hungry. But that, as they say, is a personal testimony and not a scientific finding. Too bad I’m not a rat.

The easiest way for most people to lower triglyceride levels is to adopt a very low carb diet (less than 50 grams of carbohydrate per day), then transition to a moderate carb diet devoid of most grains. Niacin and fish oil have also proven to be effective in many people, even those with genetic reasons for high triglycerides (familial hypertriglyceridemia). I combine all three approaches, and have found the eliminating any one of those results in my triglycerides rising again. Management of triglycerides in this way is done in concert with a physician and blood tests. Those with chronic health problems should check with their doctors first, of course, especially those with reduced liver or kidney function, or those suffering from conditions such as gout that require specific diets.

Resisting Resistance

Humans are adapted to eat a certain diet, and in terms of adaptation, the modern agricultural era is a blip on the radar screen. We simply haven’t had time to adapt to large quantities of grain and other carbohydrates in our diets. The inexpensive access to readily available carbohydrates is new, barely 10,000 years old, and our biological machinery is not able to handle it. That’s the philosophical framework under girding the modern low carb / paleo diet movement. The rise of leptin resistance is just one more metabolic condition that supports the effectiveness of a low carb / paleo lifestyle.

Other Resources

MegaSearch: Leptin Resistance

Heart Scan Blog: Niacin

Heart Scan Blog: Fish Oil

Cancer, Fructose and Ketogenic Diets

Dana at Hold the Toast has several articles on the problems with fructose, including the hidden fructose in Agave Nectar. Her latest post repeats the wide-spread media analysis of a recent study where fructose shows itself to be a superior fuel for pancreatic cancer cells. Unlike most of the media accounts, Dana focuses on the important part of the story:

It was the first sentence in the abstract that really caught my eye: Carbohydrate metabolism via glycolysis and the tricarboxylic acid cycle is pivotal for cancer growth, and increased refined carbohydrate consumption adversely affects cancer survival. Got that? Carbohydrates are pivotal for cancer growth. Eating carbs means you’re less likely to survive cancer. Remember that next time someone tells you you’re courting cancer by eating meat and eggs instead of grains and fruit.

Unlike some reports in the press and blogosphere elsewhere, the study doesn’t show that fructose causes pancreatic cancer or feeds cancer cells in the body. The researchers used pancreatic cancer cells for the test, isolated in petri dishes, and then added more glucose or fructose to the solutions. They were then able to measure the rate at which the cells divided and grew, and found that:

In comparison with glucose, fructose induces thiamine-dependent transketolase flux and is preferentially metabolized via the nonoxidative pentose phosphate pathway to synthesize nucleic acids and increase uric acid production.

Ah. I always suspected fructose was preferentially metabolized via the nonoxidative pentose phosphate pathway. I’ll have to have biologist or doctor sort out that sentence for me.

My understanding of the way fructose is metabolized by the liver leads me to believe a cancer cell in your pancreas would never see fructose. It would see glucose in the blood stream, which it uses to divide and grow just fine. Dr. Briffa explains:

The study in question found, in summary, that feeding cancer cells fructose caused them to proliferate. Obviously, this is not a good state of affairs. The authors of the study suggest that reducing intake of refined fructose may disrupt cancer growth.

When fructose is consumed it travels to the liver. The vast majority, if not all, of it is metabolised in the liver, meaning that little or any reaches the general circulation. However, there is always the potential that uric acid might exert a considerable direct effect on the liver. We can perhaps see the potential for fructose to be directly toxic to the liver in some evidence linking its consumption with ‘fatty liver’ (a build-up of fat within the tissue of the liver).

But what about other tissues in the body?

One of the effects of fructose is to cause a ramping up of uric acid in the liver. Uric acid is, as its name suggests, acidic. And the relevance of this is that some cancer cells grow better in an acidic environment. Now, the body has processes by which it regulates the pH (acidity/alkalinity) of the bloodstream within quite a narrow range. However, there is the potential for the pH to drop (become more acidic) and this might perhaps encourage cancer growth.

I’m not aware of any evidence linking fructose consumption and cancer in the scientific literature. However, this recent study, I think, gives us another potential reason for giving fructose and high fructose corn syrup a miss.

Those wanting to read more about fructose can follow this MegaSearch Link for all the articles by our Low Carb Daily index of websites. We select only low carb / paleo / primal sites for this search, targeting the results to the interests of our readers.

I am as eager as the next low carber to pounce on a media story that equates fructose with cancer, but let’s be honest: this study doesn’t say that. We have a duty to try and report things accurately, although for us laypeople, it can be difficult. Remember, we are critical of the old idea that eating cholesterol added cholesterol to the bloodstream. It makes sense on one level, and that would be great, except it simply isn’t true. We know that now. Why are we so quick to say eating sugar feeds cancer? We need our theory validated with research.

On the other side, the Corn Refiner’s Association (CRA) has already weighed in with a critique of the study, so the battle is engaged. And you know what? Some of their criticisms are valid.

Dietary science is the bastard son of real science, yet the mass media treats every new study like it’s E=MC2.

As Dana pointed out, the real problem is that cancer cells use glucose, and a high blood glucose level may assist in their growth. And carbs lead to high blood glucose levels. It sounds reasonable that a low carb diet would help slow cancer growth, but are there any studies showing that effect?

Well, the University of Würzburg Hospital has recommended a low carb, ketogenic diet for cancer patients since 2007. And they link a few studies on their site.

At least one other study shows that starving cancer with a very low calorie, ketogenic diet may work. This isn’t the type of diet we are on: calories were limited to 600 per day, and the ratio of fat to carbs and protein was 4:1. Italian and American researchers used this extreme, ketogenic diet and traditional treatments (radiation and chemotherapy) and mapped the progress of a particularly bad cancer: glioblastoma multiforme (brain cancer):

After two months treatment, the patient’s body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy.

This is one study, on one patient, with a very strict dietary regime that showed promise. It doesn’t mean that staying in ketosis prevents cancer, or that a different type of cancer would be slowed by the same ketogenic diet. It does point out the need for further research.

Needless to say, someone with cancer would want to discuss this approach with their doctor as an adjunct to standard treatment, and not risk “going it alone” based on this one study.