Fasting Improves Diabetic Kidney Disease

This article discusses the two studies that showed the improvement of kidney functions in those with diabetes who fasted.

An estimated 37 million Americans have Chronic kidney disease (CKD)—more than 1 in 7 U.S. adults. Kidney disease is present in about 1 in 3 people with diabetes and 1 in 5 people with high blood pressure.[1]

Fasting and the Kidneys

Everybody fasts. We fast when we sleep, and that explains the word breakfast. Intermittent fasting can be done longer—from 12 to 36 hours or sometimes days.

Periodic fasting has protective effects by reducing oxidative damage. Sugar or glucose metabolism releases reactive oxygen species that are negatively charged and cause cellular injury (oxidative damage).

The resulting damage leads to inflammation in an attempt to repair. However, if the injury is repetitive, no repair happens, and the harm to the cells continues, eventually affecting organ function. That is what happens to the kidneys.

With the current diabetes treatment, the kidneys will deteriorate over time, even with the best care. There are five chronic kidney failure stages, each taking five years.

Therefore, if you have Stage 1 right now, you could expect hemodialysis in 25 years. Or earlier if you get dehydrated or take a nephrotoxic drug or substance.

The kidneys prefer fat and ketones for their metabolism.

That is why fasting may be good for the kidneys. The body changes its fuel source from glucose to fat during a fast. Fat stores are also transformed into ketones for fuel.

Ketones burn cleaner (with less oxidation) than glucose. Less oxidation means less oxidative damage to cells. The brain can also function on ketones.

Urine Protein and Kidney Disease

The first study was done at the University Hospital of Heidelberg. Patients with type 2 diabetes with good diabetes and blood pressure control were included. All have albumin in their urine. [1]

Albumin is a protein in the blood and should not be in the urine. High amounts of albumin in the urine (albuminuria) mean a higher risk of chronic kidney disease worsening into kidney failure.

Once in kidney failure, lifelong dialysis or a kidney transplant are the only options.

Participants and Diet

Participants were randomly assigned a Fasting Mimicking Diet (study group) and a Mediterranean diet (control) for five consecutive days each month. Then they return to their usual diet until the next diet cycle.

A Fasting Mimicking Diet (FMD) is a plant-based low-calorie diet that mimics the effects of fasting on glucose and increases the ketones.

Day 1 contains 4600 kilojoules (kJ) [1099 calories] (11% protein, 46% fat, and 43% carbohydrates). Days two to five provided 3000 kJ [717 calories] (9% protein, 44% fat, and 47% carbohydrate) daily.

The Mediterranean diet (M-diet) is mainly plant-based. Whole grains, vegetables, legumes, fruits, nuts, seeds, herbs, and spices are the backbone of the diet. Olive oil is the primary source of fat.

Fish, seafood, dairy, and poultry are included in moderation. Red meat and sweets are eaten only occasionally.

The number of calories in the Mediterranean diet is the same as the participant’s caloric intake before the study.

Medication changes before the study

Fasting Mimicking diet, like intermittent fasting, decrease carbohydrate intake and can lead to low blood sugar (hypoglycemia) while on diabetes medications.

Subjects on the FMD diet had to stop their short-acting insulin and reduce the long-acting insulin by 50%.

All oral diabetes medicines were stopped during the FMD.

I talked about how to manage diabetes medications while fasting in- Intermittent fasting while on Diabetes Medications.

The participants measured their blood sugar levels using finger sticks. And even though the insulin doses were decreased, they were still adjusted as needed. Blood pressures were also monitored to know if dose changes were required.

Results

Improved insulin sensitivity

The HOMA-IR significantly improved in the FMD group. The (Homeostatic Model Assessment for Insulin Resistance) measures insulin sensitivity.

Increased insulin sensitivity means the blood sugar can quickly enter the liver and muscle cells. This results in lower blood sugars and less oxidative damage.

Weight loss in the FMD group was higher and more significant compared to the baseline and control groups.

Less drugs needed

Lower doses of insulin

After three diet cycles, insulin could be reduced in 57% of participants in the FMD group compared to 32% of the M-Diet group.

In contrast, for 5% of the participants of the M-Diet group, insulin doses had to be increased.

After six diet cycles, insulin could be reduced in 67% of participants in the FMD group compared to baseline.

In contrast, in 21% of the participants of the M-Diet group, antihyperglycemic medication had to be increased compared to baseline.

The results are consistent with another study where three participants fully weaned off insulin. The duration of intermittent fasting is more aggressive at 36 hours.  – A Case Report of 3 Diabetic Patients that are Weaned Off Insulin

Lower doses of blood pressure medicines

Blood pressure medication was reduced in 10% of the participants of the FMD group compared to 5% of the participants of the M-Diet group after three and six diet cycles.

In contrast, antihypertensive medication had to be increased in 5% of the participants of the M-Diet group after three diet cycles and 10% after six diet cycles.

Albumin in the urine

Macroalbuminuria is a urinary albumin-to-creatinine level of more than 300 mg/g Cr. Microalbuminuria is 30 to 300 mg/d.

Those in the FMD group with microalbuminuria at baseline had lower amounts of albumin in their urine. This is important since albumin in the urine predicts diabetic nephropathy in type 2 diabetes.

For those with microalbuminuria (>300 mg) at baseline, the change in the albumin amount was the same in the FMD and M-diet groups.

The reduction in albumin in the urine is comparable to the effect of SGLT-2 inhibitors like Jardiance, Invokana, and Farxiga.

Improved Kidney Function

Kidney function is measured as creatinine clearance. It is calculated using creatinine or cystatin-C.

Cystatin C may be more accurate than serum creatinine in estimating GFR and is more strongly associated with all-cause mortality and cardiovascular events.[3]

FMD led to less decline in kidney functions based on cystatin C after six diet cycles.

Another study, presented at the American Society of Nephrology, looked at 16 patients (12 are diabetic) who did intermittent fasting (IF) from four to 12 months. Eight did IF for 12 months.[4]

62.5% of patients were found to have an improvement in kidney functions (eGFR) at the end of the period of IF.

Estimated GFR is a measure of kidney functions.

The change in eGFR was found to range from 0.4 ml/min/1.73 m² to 38.8 ml/min/1.73 m²  (1.4-76.5%).[4]

The median increase in eGFR was 6.5 ml/min/1.73 m² (18.1%) during an average period of 8.8 months of IF (p-value = 0.04).[4]

Safety

FMD was well tolerated, with most participants reporting no adverse effects. The most common symptoms were weakness, muscle pain, dizziness, and headache.

Most of these symptoms can be prevented with adequate hydration and salt intake. As insulin sensitivity improves, salt and water retention are reduced and become urine.

Replacing the lost water and electrolytes is essential to prevent the “keto flu.”

Low blood sugar episodes did not differ between the study groups.

Summary

Fasting can improve insulin sensitivity, decrease the need for diabetes and hypertension medication and slow the worsening of kidney function.

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References:

1. Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2021. Centers for Disease Control and Prevention, U.S. Department of Health and Human Services; 2021.
2. Sulaj A et al. A six-month periodic fasting reduces microalbuminuria and improves metabolic control in patients with type 2 diabetes and diabetic nephropathy: a randomized controlled study. J Clin Endocrinol Metab. 2022 Jul 14;107(8):2167-2181. doi: 10.1210/clinem/dgac197. PMID: 35661214; PMCID: PMC9282263.
3. Ferguson TW, Komenda P, Tangri N. Cystatin C as a biomarker for estimating glomerular filtration rate. Curr Opin Nephrol Hypertens. 2015 May;24(3):295-300. doi: 10.1097/MNH.0000000000000115. PMID: 26066476.
4. Gunasekaran Deepthi, Dinary Buthayna A. The Effects of Intermittent Fasting on the Progression of CKD. October 22, 2020. ASN.

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